Overview
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, with fewer than 15% of patients surviving five years post-diagnosis. Resistance to radiotherapy remains a major barrier to successful treatment. Our recent research revealed a surprising culprit: meiotic synaptonemal complex (SC) proteins, normally confined to germ cells, but found by us to be aberrantly expressed in more than half of HCC cases. Their expression promotes genomic instability, uncontrolled proliferation, and treatment resistance—yet their immunological roles remain largely unexplored.
About this opportunity
This PhD project will investigate how SC protein reactivation contributes to radiotherapy resistance and whether these germline-derived proteins can serve as immunogenic targets for novel liver cancer therapies. By uncovering these mechanisms, the project will identify new therapeutic vulnerabilities that could transform treatment strategies for resistant HCC.
Research Aims:
- Define the molecular mechanisms by which meiotic proteins drive DNA damage resistance and genomic instability.
- Characterise the immune consequences of meiotic protein expression and presentation as tumour antigens.
- Develop and evaluate novel immunotherapeutic strategies targeting SC-derived neoantigens.
Techniques & Training:
This is a highly interdisciplinary project, bridging molecular biology, immunology, and clinical translation. The student will receive comprehensive training in:
- CRISPR/Cas9 genome editing to manipulate SC genes in liver cancer models.
- Single-cell and spatial transcriptomics to map SC expression and tumour microenvironmental context.
- Mass spectrometry-based immunopeptidomics to identify naturally presented SC-derived antigens.
- Functional T-cell assays to test immune recognition and response.
- High-content imaging and quantitative data analysis for mechanistic and spatial insights.
The project integrates into the ongoing PINCER clinical trial and the Liverpool ECMC biomarker discovery programme, ensuring direct clinical relevance.
Training Environment:
You will join a vibrant, well-funded research group with a proven record of supporting PhD success. The primary supervisor is an experienced EMBO Young Investigator with a track record of translating molecular discoveries into clinical trials. You will work alongside skilled postdocs, final-year PhD students, and clinical collaborators.
You will benefit from:
- Structured mentoring and regular one-to-one supervision
- Participation in an annual joint lab retreat focused on project management and collaboration
- Opportunities for international networking and training through EMBO events and partner institutions
- A diverse and inclusive research environment that supports independent, creative science
Impact:
This project links fundamental cancer biology with cutting-edge immunotherapy development. By targeting meiotic SC proteins—absent from healthy tissues but reactivated in tumours—the student will help pioneer a precision immunotherapy strategy with global clinical relevance. The research will not only deepen understanding of therapy resistance but also open new avenues for patient-specific treatments in liver cancer and beyond.
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond.
Further information on the programme and instructions on how to apply, including a link to the application portal, can be found on our website https://www.dimen.org.uk/
Further reading
1. Moonlighting Role of Meiotic SYCP1 in Breast Cancer: A Chromatin-Bound Regulator of DNA Repair, Transcription, and Drug Resistance. LC Brennan, OV Grinchuk, M Pachon, IF Sou, CJ Fawcett, CG Nogueira, M Guthrie, AD Bates, M Hine, A Thomaz, Z Hu, AB Fielding, OR Davies, W-W Tee, UL McClurg, BioRXiV, 2025
2. Sou IF, Hamer G, Tee W-W, Vader G, McClurg UL$ (2022) Cancer and meiotic gene expression – two sides of the same coin? Invited book chapter: Chapter 11 in Meiosis in Development and Disease, Current Topics in Developmental Biology 2023:151:43-68.
3. Sandhu S, Salmon LJ, Hunter JE, Wilson CL, Perkins ND, Hunter N$, Davies OR$, McClurg UL$ (2021) Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12. Communications Biology 4(1):1371
4. Sou IF, Pryce RM, Tee W-W$, McClurg UL$ (2021) Meiosis initiation – a complex story of two sexes in all creatures great and small. Invited review, Biochem J 478 (20): 3791–3805.